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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Protocols and results reviewed and accepted by the National Toxicology Program's Board of Scientific Counselor's Technical Reports Review Subcommittee, USA National Institutes of Health

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.5300 - In vitro Mammalian Cell Gene Mutation Test
Deviations:
not specified
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): sodium xylenesulfonate
- Molecular formula (if other than submission substance): no data
- Molecular weight (if other than submission substance): no data
- Substance type: organic
- Physical state: powder
- Analytical purity: 65%
- Impurities (identity and concentrations): not identified from NMR spectrum provided
- Composition of test material, percentage of components: 11.5% ortho, 38% meta, 15.5% para
- Purity test date: February 13, 1986
- Lot/batch No.: RO92085 / 03
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable
- Storage condition of test material: glass bottles with Teflon lined caps or double bagged in metal drums at room temperature in the dark
- Other:

Method

Target gene:
mouse lymphoma cells - TK locus
Species / strain
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
125, 250, 500, 1000 and 2500 microgram active ingredient per milliliter
Vehicle:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controls
Negative controls:
yes
Solvent controls:
yes
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
Migrated to IUCLID6: without S9 and methlcholanthrene with S9
Details on test system and conditions:
METHOD OF APPLICATION: in Fischer medium

DURATION
Normal cycling time for L5178Y cells was 10 hours. Treated cultures contained 6 x 10-6 cells in 10mL medium.
Incubation with test substance continued for 4 hours, at which time the medium plus test substance was removed and the cells were resuspended in fresh medium and incubated for an additional 2 days to express the mutant phenotype. Cell density was maintained at log phase growth. After the 48-hr expression period, cells were plated in medium and soft agar supplemented with TFT (trifluorothymidine) for selection of TFT-resistant cells. Cells were plated in nonselective medium and soft agar to determine cloning efficiency. Plates were incubated at 37 degrees C in 5% CO2 for 10-12 days.


NUMBER OF REPLICATIONS: each treatment level was replicated, including positive and solvent controls


OTHER:
Evaluation criteria:
Minimum criteria for accepting an experiment as valid are presented in Caspary et al 1988
Statistics:
All data were evaluated statistically for trend and peak responses. Both responses had to be significant (P<=0.05) for the test substance to be considered positive; i.e., capable of inducing TFT resistance. A single significant response led to a "questionable" conclusion, and absence of both a trend and a peak response resulted in a "negative" conclusion.

Results and discussion

Test results
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
no, but tested up to limit concentrations
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: strain/cell type: L5178Y
Remarks:
Migrated from field 'Test system'.
Additional information on results:
Negative in one replicate series and positive in other replicate series with metabolic activation; leads to "equivocal" conclusion with metabolic activation

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative without metabolic activation questionable with metabolic activation

Not mutagenic without metabolic activation, equivocal with metabolic activation